Previous studies have reported an association between human sirtuins' single-nucleotide polymorphisms (SNPs) and Alzheimer's disease (AD) susceptibility in the apolipoprotein E (APOE) ε4-negative population, although the findings are inconsistent. To obtain a more precise estimation of this relationship, we conducted a meta-analysis to assess the association between the rs10410544 C/T polymorphism of SIRT2 and the risk of AD with APOE ε4 status. We searched all relevant PubMed publications and included three studies in our meta-analysis involving a total of 1,794 patients and 2,054 control subjects. Odds ratios (ORs) with 95% confidence intervals (CIs) were employed to evaluate the association of the SIRT2 SNP with AD susceptibility, and we analyzed the extracted data stratified by the APOE ε4-carrying status. Overall, the results show that the SIRT2 SNP is associated with human AD risk in the comparison models (T vs. C: OR 1.140, 95% CI 1.034-1.258; TC vs. CC: OR 1.178, 95% CI 1.019-1.361; TT + TC vs. CC: OR 1.197, 95% CI 1.043-1.373). In the stratified analyses, the European population had a significantly increased risk of AD (T vs. C: OR 1.110, 95% CI 1.002-1.229), and we also observed a significant association in the APOE ε4-negative population (T vs. C: OR 1.165, 95% CI 1.025-1.324; TT + TC vs. CC: OR 1.222, 95% CI 1.022-1.461). This meta-analysis indicates that the presence of the SIRT2 SNP with APOE ε4-negative status contributes to the development of AD in humans Epidemiological studies of larger sample sizes are warranted to confirm this hypothesis.